Our objective is to study the DNA damage and repair in individual genes and in non-coding sequences within the genome. This is correlated to more traditional studies of DNA repair as an average over the genome. Findings reviewed in Bohr VA, Phillips DH and Hanawalt PC, Cancer Res. 47: 6426-6436, 1987, have indicated that active genes are preferentially repaired in mammalian cells and that determinations of DNA repair in specific genes are important for correlations to biological endpoints and risk assessments. Whereas our earlier studies were limited to UV as a damaging agent, we have now developed an approach which can be employed for a large variety of bulky agents that react with the DNA. We are currently further developing techniques that measure damage and repair of alkylating agents in specific genes including oncogenes. We are studying preferential repair of genes in a number of human, cancer prone DNA repair deficient syndromes and in various human and rodent mutant cell lines, some of which are transfected with repair genes. We have found that transfection of a UV sensitive CHO cell line with the human repair gene, ERCC 1 restores preferential repair in the cells.